Enriching cancer pharmacology with drugs of marine origin

Abstract

Marine natural products have proven, over the last half-century, to be effective biological modulators. These molecules have revealed new targets for cancer therapy as well as dissimilar modes of action within typical classes of drugs. In this scenario, innovation from marine-based pharmaceuticals has helped advance cancer chemotherapy in many aspects, as most of these are designated as first-in-class drugs. Here, by examining the path from discovery to development of clinically approved drugs of marine origin for cancer treatment-cytarabine (Cytosar-U®), trabectedin (Yondelis®), eribulin (Halaven®), brentuximab vedotin (Adcetris®), and plitidepsin (Aplidin®)-together with those in late clinical trial phases-lurbinectedin, plinabulin, marizomib, and plocabulin-the present review offers a critical analysis of the contributions given by these new compounds to cancer pharmacotherapy. 1 | INTRODUCTION Natural products have long been used in the treatment of human maladies and set a strong foundation upon which modern pharmacology has been erected. Particularly for cancer treatment, chemotherapeutic agents of natural origin have remarkably impacted the field, not only for their clinical importance but also for allowing the expansion of knowledge in cancer pharmacology. Natural agents like doxorubicin, paclitaxel, vincristine, and vinblastine are commonly used as first-line treatments for several cancers. The compounds of marine origin have a more recent history. Nevertheless, studies have shown their unique

Anticancer Potential of Compounds from the Brazilian Blue Amazon

“…Indeed, the Salinispora have attracted much attention as these obligate marine bacteria house unique biosynthetic pathways and, therefore, are a prolific spring of natural products [151]. Specifically, the species S. tropica is the producer of marizomib, a b-lactone-g-lactam proteasome inhibitor that is currently undergoing phase III clinical trials for the treatment of glioblastoma and multiple myeloma [14]. Following this hint, further studies then confirmed the occurrence of Salinispora sp.…”

“…From the natural products perspective, ascidians are among the best-studied groups and evidence has shown them, and their associated microorganisms, to abound in inventive chemistry with interesting bioactivity [80,81]. Three ascidian-sourced molecules have made it all the way to the clinics and figure among the list of drugs available for cancer treatment (reviewed by [14]). Trabectedin (ET-743), a peculiar kind of DNA alkylator, is an alkaloid obtained from Ecteinascidia turbinata Herdman, 1880 (Perophoridae) and the active principle of Yondelis, a chemotherapeutic agent used for treating soft tissue sarcoma since 2007 [82,83].…”

“…Lurbinectedin, an analogue thereof, has just recently been approved for the treatment of metastatic small cell lung cancer as Zepzelca [84]. The cyclic depsipeptide plitidepsin (aplidin, dehydrodidemnin B), isolated from Aplidium albicans (Milne Edwards, 1841) (Polyclinidae), is a quite unusual inhibitor of protein synthesis that makes up Aplidin, approved in late 2018 for the treatment of multiple myeloma [14,85,86].…”

“…Especially for anticancer therapy, in recent years, compounds from marine sources have already shown a great impact, as tackling such disease is the purpose of 8 out of the 13 approved marine-based drugs. Each of these medicines conveys remarkable courses of development, which have, moreover, instructed scientists on overcoming issues related to supply and toxicity [14].…”

Origins and Bioactivities of Natural Compounds Derived from Marine Ascidians and Their Symbionts

“…Didemnins A-C (19-21) ( Figure 11) were initially identified from ascidian symbiotic microbes. Among them, didemnin B (20), with a high cytotoxicity activity, was the first marine natural product to be utilized in clinical trials [64].…”